Gavin, Rosen, Chase, Grayson, Tun, Sharma — The Psychiatric Institute, University of Illinois at Chicago; Gavin, Rosen, Grayson, Sharma — Department of Psychiatry, University of Illinois at Chicago College of Medicine, Chicago, Ill.

Abstract

Background: A restrictive chromatin state has been thought to be operant in the pathophysiology of schizophrenia. Our objective was to ascertain whether differences exist between baseline levels of a repressive chromatin mark such as dimethylated lysine 9 of histone 3 (H3K9me2) in patients with schizophrenia and healthy controls and whether a histone deacetylase (HDAC) inhibitor in an in vitro assay would differentially affect chromatin structure based on diagnosis

Methods: We obtained blood samples from 19 healthy controls and 25 patients with schizophrenia and isolated their lymphocytes. We measured baseline H3K9me2 levels (normalized to total histone 1) in the lymphocytes from all participants via Western blot analysis. To examine the effects of an HDAC inhibitor on H3K9me2, we cultured the lymphocytes from participants with trichostatin A (TSA) for 24 hours and then measured changes in H3K9me2 relative to the control
condition (dimethyl sulfoxide).

Acknowledgements: We would like to thank Saritha Kartan for her technical assistance, as well as Drs. Henry Dove, Mark Rasenick and Robert Marvin for departmental support. Individual investigators were supported by PHS grants MH067631 (D.P.G.) and MH62682 (D.R.G.).